The effects of various DNA damaging agents were compared in human skin fibroblasts and hyman bronchial epithelial and fibroblast cells. The three cell types exhibited the same (1) rate of repair of DNA single strand breaks (SSB) after irradiation, (2) rate of excision repair after UV-irradiation, and (3) level of SSB after exposure to 7,12-dimethylbenz[a]anthracene, benzo[a]pyrene diol epoxide (BPDE), and N-methyl-N'-nitro-N-nitrosoguanidine. Since formaldehyde is formed in equimolar quantities with methylcarbonium ions during the metabolic activation of N-nitrosodimethylamine, we have recently examined the effects of formaldehyde on the repair of the promutagenic lesion, 06-methylguanine, formed following N-nitrosodimethylamine metabolism. Formaldehyde decreases 06-transalkylase acitvity, inhibits the removal of 06-methylguanine, and, in low concentrations, synergistically potentiates the cytotoxicity and mutagenicity of N-methyl-N-nitrosourea. In high doses, 100 or 130 micromolar formaldehyde is detectably mutagenic itself. Therefore, exposure to formaldehyde may lead to the dual genotoxic mechanism of both directly damaging DNA and inhibiting repair of mutagenic and carcinogenic lesions caused by alkylating agents and physical carcinogens.